Computational Biology - Publications

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Browsing Computational Biology - Publications by Author "Ahmed, Niyaz"
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    AmpliBASE MT™: A Mycobacterium tuberculosis diversity knowledgebase
    ( 2004-04-12) Majeed, Ahmed A. ; Ahmed, Niyaz ; Rao, K. Rajender ; Ghousunnissa, S. ; Kauser, Farhana ; Bose, Buddhaditta ; Nagarajaram, H. A. ; Katoch, V. M. ; Cousins, Debby V. ; Sechi, Leonardo A. ; Gilman, Robert H. ; Hasnain, Seyed E.
    Summary: AmpliBASE MT™ is an online databank of high-resolution DNA fingerprints representing fluorescent amplified fragment length polymorphism (FAFLP) profiles or amplitypes developed for the Mycobacterium tuberculosis complex strains from 48 different countries. AmpliBASE MT™ is based on a relational database management system that is hyperlinked to visualize genotyping results in the form of DNA fingerprint images for individual strains. A flexible search system based on systematic comparisons of fragment sizes in base pairs allows inter-laboratory comparison of FAFLP profiles. Besides this, the database also displays previously published data on IS6110 profiles, spoligotypes, MIRU-VNTRs and large sequence polymorphisms along with the FAFLP records that will give the overall comparisons. Being the first of its kind, AmpliBASE MT™ is expected to be a very helpful tool in strengthening the concept of'geographic genomics'and will be very helpful to molecular epidemiologists and those interested in diagnostic development for tuberculosis. © Oxford University Press 2004; all rights reserved.
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    Disease-causing mutations in proteins: Structural analysis of the CYP1b1 mutations causing primary congenital glaucoma in humans
    ( 2006-01-01) Achary, Malkaram S. ; Reddy, Aramati B.M. ; Chakrabarti, Subhabrata ; Panicker, Shirly G. ; Mandal, Anil K. ; Ahmed, Niyaz ; Balasubramanian, Dorairajan ; Hasnain, Seyed E. ; Nagarajaram, Hampapathalu A.
    In this communication, we report an in-depth structure-based analysis of the human CYP1b1 protein carrying disease-causing mutations that are discovered in patients suffering from primary congenital glaucoma (PCG). The "wild-type" and the PCG mutant structures of the human CYP1b1 protein obtained from comparative modeling were subjected to long molecular dynamics simulations with an intention of studying the possible impact of these mutations on the protein structure and hence its function. Analysis of time evolution as well as time averaged values of various structural properties - especially of those of the functionally important regions: the heme binding region, substrate binding region, and substrate access channel - gave some insights into the possible structural characteristics of the disease mutant and the wild-type forms of the protein. In a nutshell, compared to the wild-type the core regions in the mutant structures are associated with subtle but significant changes, and the functionally important regions seem to adopt such structures that are not conducive for the wild-type-like functionality. © 2006 by the Biophysical Society.
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    Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees
    ( 2002-05-13) Panicker, Shirly G. ; Reddy, Aramati B.M. ; Mandal, Anil K. ; Ahmed, Niyaz ; Nagarajaram, Hampapathalu A. ; Hasnain, Seyed E. ; Balasubramanian, Dorairajan
    PURPOSE. To determine the possible molecular genetic defect underlying primary congenital glaucoma (PCG) in India and to identify the pathogenic mutations causing this childhood blindness. METHODS. Twenty-two members of five clinically well-characterized consanguineous families were studied. The primary candidate gene CYP1B1 was amplified from genomic DNA, sequenced, and analyzed in control subjects and patients to identify the disease-causing mutations. RESULTS. Five distinct mutations were identified in the coding region of CYP1B1 in eight patients of five PCG-affected families, of which three mutations are novel. These include a novel homozygous frameshift, compound heterozygous missense, and other known mutations. One family showed pseudodominance, whereas others were autosomal recessive with full penetrance. In contrast to all known CYP1B1 mutations, the newly identified frameshift is of special significance, because all functional motifs are missing. This, therefore, represents a rare example of a natural functional CYP1B1 knockout, resulting in a null allele (both patients are blind). CONCLUSIONS. The molecular mechanism leading to the development of PCG is unknown. Because CYP1B1 knockout mice did not show a glaucoma phenotype, the functional knockout identified in this study has important implications in elucidating the pathogenesis of PCG. Further understanding of how this molecular defect leads to PCG could influence the development of specific therapies. This is the first study to describe the molecular basis of PCG from the Indian subcontinent and has profound and multiple clinical implications in diagnosis, genetic counseling, genotype-phenotype correlations and prognosis. Hence, it is a step forward in preventing this devastating childhood blindness.